Current computational methods for enzyme design

2021 ◽  
Vol 35 (09) ◽  
pp. 2150155
Author(s):  
Talmage L. Coates ◽  
Naomi Young ◽  
Austin J. Jarrett ◽  
Connor J. Morris ◽  
James D. Moody ◽  
...  
Keyword(s):  
Computational Methods ◽  
Design Methods ◽  
Enzyme Design ◽  
Traditional Methods ◽  
Computational Approaches ◽  
Computational Enzyme Design ◽  
Experimental Approaches

Computational enzyme design has made great strides over the last five years. Traditional methods of enzyme design require synthesis and evaluation of many mutations. Computational enzyme design has emerged as a powerful tool to predict how specific mutations modify a protein’s activity, stability, and/or selectivity. Such computational approaches can evaluate many mutations and reduce the load of in vitro work by identifying mutations likely to accomplish design objectives. Computational approaches can explore mutational spaces inaccessible in traditional mutagenesis. Computational methods reduce cost and time compared with experimental approaches. We review the efficacy and key differences of computational enzyme design methods as published in recent studies. The included articles used computational methods to design enzymes, were published no earlier than 2015, met design objectives, and verified results in vitro.

scholarly journals The wiring of protein networks: Computational approaches for predicting protein interaction networks

2011 ◽  
Vol 33 (1) ◽  
pp. 8-11
Author(s):  
Hung Xuan Ta ◽  
Liisa Holm
Keyword(s):  
Computational Methods ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Protein Interaction Networks ◽  
Interaction Networks ◽  
Experimental Techniques ◽  
Biological Functions ◽  
Protein Protein Interactions ◽  
Computational Approaches ◽  
Experimental Approaches

A great number of cellular behaviours are mediated by proteins which always carry out their functions by interacting with each other. Unravelling protein–protein interactions (PPIs) is one of the central goals in proteomics, which will decipher the molecular mechanisms underlying the biological functions and thereby help to understand human diseases on a system-wide level. A number of experimental techniques, especially high-throughput approaches, have resulted in a large amount of PPI data that still suffer from incompleteness and contradiction. Moreover, these experimental techniques are expensive, time-consuming and labour-intensive. Computational methods have emerged as complementary tools to experimental approaches to discover PPIs. Promisingly, computational methods can guide, assess and validate experimental data and finally predict novel PPIs.

Computational Approaches to Predict the Non-canonical DNAs

2019 ◽  
Vol 14 (6) ◽  
pp. 470-479 ◽  
Author(s):  
Nazia Parveen ◽  
Amen Shamim ◽  
Seunghee Cho ◽  
Kyeong Kyu Kim
Keyword(s):  
Computational Methods ◽  
Genetic Instability ◽  
Computational Prediction ◽  
Structure And Function ◽  
Sequence Motifs ◽  
Computational Approaches ◽  
Functional Roles ◽  
And Function ◽  
Genetic Events ◽  
Insight Into

Background: Although most nucleotides in the genome form canonical double-stranded B-DNA, many repeated sequences transiently present as non-canonical conformations (non-B DNA) such as triplexes, quadruplexes, Z-DNA, cruciforms, and slipped/hairpins. Those noncanonical DNAs (ncDNAs) are not only associated with many genetic events such as replication, transcription, and recombination, but are also related to the genetic instability that results in the predisposition to disease. Due to the crucial roles of ncDNAs in cellular and genetic functions, various computational methods have been implemented to predict sequence motifs that generate ncDNA. Objective: Here, we review strategies for the identification of ncDNA motifs across the whole genome, which is necessary for further understanding and investigation of the structure and function of ncDNAs. Conclusion: There is a great demand for computational prediction of non-canonical DNAs that play key functional roles in gene expression and genome biology. In this study, we review the currently available computational methods for predicting the non-canonical DNAs in the genome. Current studies not only provide an insight into the computational methods for predicting the secondary structures of DNA but also increase our understanding of the roles of non-canonical DNA in the genome.

scholarly journals Discovery of vanoxerine dihydrochloride as a CDK2/4/6 triple-inhibitor for the treatment of human hepatocellular carcinoma

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Ying Zhu ◽  
Kun-Bin Ke ◽  
Zhong-Kun Xia ◽  
Hong-Jian Li ◽  
Rong Su ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle Progression ◽  
G1 Arrest ◽  
Huh7 Cells ◽  
Synergistic Cytotoxicity ◽  
Combination Study ◽  
Experimental Approaches ◽  
Induced Apoptosis

Abstract Background Cyclin-dependent kinases 2/4/6 (CDK2/4/6) play critical roles in cell cycle progression, and their deregulations are hallmarks of hepatocellular carcinoma (HCC). Methods We used the combination of computational and experimental approaches to discover a CDK2/4/6 triple-inhibitor from FDA approved small-molecule drugs for the treatment of HCC. Results We identified vanoxerine dihydrochloride as a new CDK2/4/6 inhibitor, and a strong cytotoxicdrugin human HCC QGY7703 and Huh7 cells (IC50: 3.79 μM for QGY7703and 4.04 μM for Huh7 cells). In QGY7703 and Huh7 cells, vanoxerine dihydrochloride treatment caused G1-arrest, induced apoptosis, and reduced the expressions of CDK2/4/6, cyclin D/E, retinoblastoma protein (Rb), as well as the phosphorylation of CDK2/4/6 and Rb. Drug combination study indicated that vanoxerine dihydrochloride and 5-Fu produced synergistic cytotoxicity in vitro in Huh7 cells. Finally, in vivo study in BALB/C nude mice subcutaneously xenografted with Huh7 cells, vanoxerine dihydrochloride (40 mg/kg, i.p.) injection for 21 days produced significant anti-tumor activity (p < 0.05), which was comparable to that achieved by 5-Fu (10 mg/kg, i.p.), with the combination treatment resulted in synergistic effect. Immunohistochemistry staining of the tumor tissues also revealed significantly reduced expressions of Rb and CDK2/4/6in vanoxerinedihydrochloride treatment group. Conclusions The present study isthe first report identifying a new CDK2/4/6 triple inhibitor vanoxerine dihydrochloride, and demonstrated that this drug represents a novel therapeutic strategy for HCC treatment.

In vitro assessment of food-derived-glucose bioaccessibility and bioavailability in bicameral cell culture system

2020 ◽  
Vol 45 (5) ◽  
pp. 631-637
Author(s):  
Cansu Ozel-Tasci ◽  
Gozde Pilatin ◽  
Ozgur Edeer ◽  
Sukru Gulec
Keyword(s):  
Cell Culture ◽  
Culture System ◽  
Metabolic Diseases ◽  
Enzymatic Digestion ◽  
Cell Culture System ◽  
Culture Studies ◽  
Experimental Approaches ◽  
In Vitro Assessment

AbstractBackgroundFunctional foods can help prevent metabolic diseases, and it is essential to evaluate functional characteristics of foods through in vitro and in vivo experimental approaches.ObjectiveWe aimed to use the bicameral cell culture system combined with the in vitro digestion to evaluate glucose bioavailability.Materials and methodsCake, almond paste, and pudding were modified by adding fiber and replacing sugar with sweeteners and polyols. Digestion process was modeled in test tubes. Rat enterocyte cells (IEC-6) were grown in a bicameral cell culture system to mimic the physiological characteristics of the human intestine. The glucose bioaccessibility and cellular glucose efflux were measured by glucose oxidase assay.Results and discussionThe glucose bioaccessibilities of modified foods were significantly lower (cake: 2.6 fold, almond paste: 9.2 fold, pudding 2.8 fold) than the controls. Cellular glucose effluxes also decreased in the modified cake, almond paste, and pudding by 2.2, 4, and 2 fold respectively compared to their controls.ConclusionOur results suggest that combining in vitro enzymatic digestion with cell culture studies can be a practical way to test in vitro glucose bioaccessibility and bioavailability in functional food development.

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